The work presented in this research proposal is designed to aid in the development of methods for the treatment and prevention of arthritis following bacterial joint infection. The experimental approach relies on the use of animal models, in vitro bacterial and cartilage cultures, and analytical biochemical assays for quantitation of short-term bacterial effects on cartilage. By examining cartilage stability through quantitation of its constituent molecules, collagen and glycosaminoglycans, early evidence of degeneration caused by bacterial infections will be established. Using such changes as an assay procedure, the ability of antibiotic treatments to block or reverse deleterious bacterial effects will be analyzed directly in in vivo animal models. More direct approaches to the possible mechanisms by which the bacteria cause cartilage destruction will be carried out in in vitro analysis. Clinical isolates of bacteria will be analyzed for glycosaminoglycan degradative activity. Organ cultures of cartilage will be challenged by direct bacterial inoculation under varying conditions to characterize the effect of bacteria on the chondrocytes and surrounding matrix without participation of the immune system.